Project Summary/Abstract The rapid rise in prenatal exposure to prescription and other opioids over the last decade mirrors dramatic trends in opioid use across the general population of the US. In some states nearly one in four pregnancies are exposed to prescription opioids; 60-80% of affected pregnancies are Medicaid-covered. Moreover, the rise in maternal opioid use disorder (OUD), prenatal opioid exposure, and neonatal abstinence syndrome (NAS) appears to be driving a substantial increase child protective services (CPS) involvement. However, the impact of prenatal opioid exposure on pregnancy and child outcomes, independent of co-occurring factors, remains unclear. To address this gap, we have assembled a multi-source longitudinal administrative birth cohort that links data for all ~800,000 live births across Wisconsin, including ~350,000 Medicaid-covered births, from 2007 to 2018. By linking data at the individual-level, and updating each source of data annually, we can identify and track subsequent births (siblings) and follow a growing cohort of mothers and their children as their lives unfold over more than a decade. Our unique data support multilevel examination of individual factors, and the influence of health care and community characteristics, that is needed to better understand and address the effects of the opioid epidemic on women and their children. We will use regression-based and quasi-experimental methods, and geospatially informed analyses, to examine outcomes and factors which may influence outcomes. Our specific aims are: 1) Estimate the bounded annual prevalence of prenatal opioid exposure, including OUD and infant NAS, among all Medicaid-covered births in Wisconsin from 2007-2018, and describe the characteristics of affected women, families, and their communities, and changes therein over time; 2) Examine associations of prenatal opioid exposure, including OUD and NAS, with behaviors and outcomes including a) adverse pregnancy and birth outcomes; b) child maltreatment reports, substantiated reports, and foster care entries; and c) reproductive, health, social, educational, and economic outcomes for mothers and children, spanning the prenatal period through the first 8 years of the child?s life; 3) Investigate individual and community-level factors associated with maternal participation in addiction treatment during the prenatal and postpartum periods, including type(s) of treatment and treatment retention; and 4) Estimate plausibly causal effects of addiction treatment participation on maternal and child wellbeing spanning the child?s birth through age 8 using a quasi-experimental design. This research addresses the HHS 5-Point Strategy to Combat the Opioid Crisis, with a call for Better Data and Better Research, and complements the research into the biological pathways and treatment strategies enabled by the Trans NIH effort Helping to End Addiction Long-termSM (HEAL) Initiative.